Vitamin B3 (Niacin) — Rich Foods, Structure, Benefits, and Deficiency
Introduction
Vitamin B3, or niacin, is a water-soluble B vitamin; the term niacin is generic and refers to nicotinic acid, nicotinamide (niacinamide), and other derivatives. Vitamin B3 is found in bran, yeast, eggs, red meat, poultry, fish, peanuts, whole grains, legumes, and seeds.
Lack of vitamin B3 can cause pellagra and it may be prescribed during some cases of dyslipidemia (harmful changes in lipid profile). It has been used to manage the lipid profile since 1955 and is considered the oldest pleiotropic blood lipid-lowering agent (1, 2, 3).
Table of contents
Structure
Vitamin B3 has a simple molecular structure consisting of a pyridine ring with a carboxyl group attached to it.
Absorption & Metabolism
Most vitamin B3 and its metabolically active forms are absorbed in the small intestine, while some amounts are absorbed in the stomach.
Vitamin B3 is converted to the nicotinamide adenine dinucleotide (NAD) coenzyme, its main active form in the organism. NAD is required for over 400 enzymatic reactions in the body. Another active form, NAD’s phosphate analog, nicotinamide adenine dinucleotide phosphate (NADP), is present in all tissues except the skeletal muscles.
NAD and NADP are required in many metabolic redox processes: NAD is primarily involved in cellular energy metabolism and critical cellular functions (genome integrity, gene expression control, and cellular communication), whereas NADP is involved in the synthesis of cholesterol and fatty acids and maintains cellular antioxidant function.
Most dietary vitamin B3 is nicotinic acid and nicotinamide; NAD and NADP may also be found in small amounts. Some amounts of the amino acid tryptophan are converted to NAD in the body; thus, it is also a vitamin B3 source.
Vitamin B3 is almost completely absorbed. Physiological amounts of vitamin B3 are converted to NAD. Excess amounts are taken by red blood cells or methylated in the liver and excreted in the urine (1).
Recommended Intakes
According to the 2020-2025 Dietary Guidelines for Americans, the recommended dietary allowance (RDA) of vitamin B3 is 14mg for adult women and 16mg for adult men (4).
The table below shows the RDAs of vitamin B3 based on sex, age, and physiological changes during pregnancy and lactation (1, 4).
| 2-3 years | 4-8 years | 9-13 years | 14-18 years | 18+ years | |
| Male | 6mg | 8mg | 16mg | 16mg | 16mg |
| Female | 6mg | 8mg | 12mg | 12mg | 12mg |
| Pregnancy | - | - | - | 18mg | 18mg |
| Lactation | - | - | - | 17mg | 17mg |
Vitamin B3 Rich Foods
Vitamin B3 is found in many animal products, providing 5-10mg per serving, mainly in the forms of NAD and NADP. On the other hand, plant-based products provide 2-5mg per serving, mainly in the form of nicotinic acid (1).
In some grains, vitamin B3 is bound to other molecules, decreasing its bioavailability to 30%. Artificially added vitamin B3 (bread, cereals, infant formulas) is in its free form and highly bioavailable.
The table below shows foods rich in vitamin B3 and its value per serving of each food.
| Food Name | Vitamin B3 per Serving Size |
| Tuna, yellowfish, cooked | 18.8mg in 3 oz |
| Beef liver, cooked | 14.9mg in 3 oz |
| Turkey, skin and meat, cooked | 8.13mg in 3 oz |
| Chicken, skin and meat, cooked | 7.22mg in 3 oz |
| Pork liver, cooked | 7.17mg in 3 oz or 85g |
| Salmon, Atlantic, cooked | 6.83mg in 3 oz |
| Brown rice, long-grain, cooked | 5.17mg in 1 cup (202g) |
| Peanuts | 3.43mg in 1 oz (28.35g) |
| Chicken wing, cooked | 2.58mg in 1 wing or 50g |
| Rice, long-grain, cooked | 2.34mg in 1 cup (158g) |
| Lentils, cooked | 2.1mg in 1 cup (198g) |
| Potatoes, baked | 2.09mg in 1 NLEA serving (148g) |
| White bread | 1.39mg in 1 slice (30g) |
| Chickpeas (garbanzo beans), cooked | 0.86mg in 1 cup (164g) |
| Soybeans, cooked | 0.69mg in 1 cup (172g) |
Tryptophan is also considered a source of biologically active NAD, with an estimated efficiency of 1:60 (i.e., 1mg vitamin B3 = 60mg tryptophan) (1).
Vitamin B3 & Health Benefits
Cardiovascular Health
High doses of nicotinic acid (but not nicotinamide), taken for months, are used to treat dyslipidemia or imbalances in lipid profiles: vitamin B3 increases HDL or “good” cholesterol levels up to 30% and reduces LDL or “bad” cholesterol levels up to 25%, triglyceride levels by 20-50%, and lipoprotein(a) levels by 10-30% (1, 4).
These changes are expected to decrease the risk of cardiac events, such as heart attacks and strokes; however, there’s a disagreement regarding the value of nicotinic acid in treating heart disease, especially due to its side effects.
In the largest clinical trial of nicotinic acid to date, involving over 25,500 adults aged 50 to 80 (83% men) with heart disease and on statin therapy, participants were randomized to add 2g daily nicotinic acid (along with a medication to reduce the vitamin’s side effects). They had reduced LDL cholesterol and triglyceride levels and increased HDL cholesterol levels but didn’t have reduced rates of major vascular events compared to those taking only statins. Moreover, those taking nicotinic acid had a greater risk of diabetes, stomach problems, diarrhea, bleeding from the gut and brain, ischemic stroke, as well as skin rashes and ulcerations.
Additionally, two systematic reviews involving around 75,000 participants found that nicotinic acid does not protect from atherosclerotic heart disease (1).
A 2018 review of three trials with around 29,000 individuals noted that those taking 1-3g extended-release nicotinic acid daily (added to statin therapy) had a 10% increased risk of all-cause mortality than the ones taking only statins.
Stanley Hazen, MD, senior author of a recently published Nature study, said, “I'm not suggesting we should completely avoid niacin—it is an essential nutrient, but our results suggest that too much may be harmful” (5, 6).
According to the American College of Cardiology and the American Heart Association’s 2018 report, even though vitamin B3 might be useful in some cases of severe elevations in blood triglyceride levels, it has mild LDL-cholesterol-lowering effects. It is not recommended as an add-on to statin therapy (1).
Neurological and Cognitive Health
Vitamin B3 deficiency may manifest with symptoms resembling neurodegenerative and mental disorders, such as dementia and depression. Various studies have noted the importance of vitamin B3, primarily nicotinamide, in the growth and maintenance of the central nervous system or CNS (7).
Vitamin B3 accelerates the differentiation of embryonic stem cells into neural progenitors, which later become GABAergic neurons. Vitamin B3 also promotes the survival rates of neurons, especially during oxidative stress.
A population-based study in Chicago suggested that dietary vitamin B3 (nicotinamide) may protect against Alzheimer’s disease and age-related cognitive decline. The positive effects of vitamin B3 on Alzheimer’s may be related to neurotransmission, learning, and memory (7).
Vitamin B3 might ameliorate multiple sclerosis (MS) by regulating cholesterol recycling, followed by the uptake of lipid-rich myelin by white blood cells.
Niacin might have neuroprotective effects and modify the pathology of Parkinson’s disease: decreased inflammation, dopamine supplementations, and reduced oxidative stress. Low-dose vitamin B3 supplementation might reduce the risk of developing Parkinson’s disease or improve motor ability.
In animal models with glioblastomas, the most common tumors in the central nervous system, treatment with vitamin B3 led to beneficial immune modulation and increased myeloid cells’ tumor-fighting abilities (8).
Chronic Kidney Disease
Vitamin B3 is known to decrease elevated blood phosphate levels (hyperphosphatemia), one of the main features of chronic kidney disease (CKD). Hyperphosphatemia may lead to changes in vascular smooth muscle cells and promote calcification.
One retrospective study showed improved glomerular filtration rate (GFR), a test for checking how the kidneys work, and decreased serum creatinine after 24-week low-dose niacin supplementation in people with CKD (9).
Skin Health & Cancer
Nicotinamide at 4-5% concentrations is used in cosmetics to control skin aging and pigmentation. According to several clinical trials, vitamin B3 might help protect from skin aging in terms of wrinkles, skin elasticity, and color (10).
Both topical and oral, nicotinamide reduces immune suppression and cell damage caused by UV light and reduces the risk of developing non-melanoma skin cancers. Current evidence notes nicotinamide’s ability to reduce the risk of non-melanoma skin cancer and actinic keratosis (precancer) in high-risk individuals (11, 12).
It may also improve the symptoms of pruritus, rosacea, acne, and some autoimmune skin conditions (11).
Vitamin B3 Deficiency: Symptoms, Risk Groups, & Pellagra
Several groups of people are at risk of developing vitamin B3 deficiency (1):
- People with low intake of nutrients or alcohol use disorder
- People with eating disorders
- People with gastrointestinal disorders, such as Crohn’s disease, ulcerative colitis, chronic pancreatitis, liver cirrhosis
- People with low intake of vitamins B2, B6, and iron, as it may decrease tryptophan conversion to vitamin B3
- People with Hartnup disease, a rare genetic disorder affecting the kidneys, intestines, and cellular transport of tryptophan.
- People with carcinoid syndrome, as it affects tryptophan metabolism
- People taking certain medications (mentioned below).
Vitamin B3 deficiency is also known as pellagra. Pellagra commonly manifests with a triad of symptoms called “three Ds” and includes dermatitis, dementia, and diarrhea.
The main characteristics of skin manifestations are pigmented rash or brown discoloration of sunlight-exposed skin, which is sunburned-like and roughened. Neurological symptoms may include depression, anxiety, apathy, headaches, fatigue, memory loss, poor concentration, irritability, muscle weakness, and, in rare cases, aggressive, paranoid, and suicidal behavior and hallucinations. The gastrointestinal symptoms may include red tongue, nausea, vomiting, glossitis, stomatitis, abdominal pain, stomach disturbances, constipation, or diarrhea.
Niacin deficiency is rarely seen in industrialized countries but is rather limited to individuals living in poverty (1, 13).
Vitamin B3 Toxicity
Intake of high doses of niacin supplements or medications is associated with adverse effects (1, 2):
- High doses of nicotinic acid cause flushing (a warmth sensation and skin redness). The face, arms, and chest become red due to the widening of small blood vessels under the skin. A burning, tingling, and itching sensation may also be present.
- Hypotension or low blood pressure and increased risk of fatigue. High-dose vitamin B3 may also result in arrhythmias. Those with supraventricular tachycardias (SVTs) may have unusual chest sensations and palpitations even when the arrhythmia is under control.
- Impaired glucose tolerance and insulin resistance, resulting in increased fasting blood glucose levels.
- Gastrointestinal disturbances, such as nausea, heartburn, pain, and aggravated peptic ulcer disease.
- Vision problems, such as blurred or impaired vision and swollen macula.
- Liver injury leading to elevations in liver function tests. Liver injury more commonly occurs due to the use of extended-release forms of the vitamin.
- Hyperuricemia may be another side effect of high-dose niacin; thus, vitamin B3 is avoided in individuals with a history of gout.
Compared to nicotinic acid, nicotinamide is not linked to skin flushing, has fewer adverse effects, and is required in higher doses to cause toxicity.
Due to the adverse effects of vitamin B3 supplementation, the American College of Cardiology (ACG) and the American Heart Association (AHA) recommend measuring liver function tests, fasting blood glucose or HbA1c, and uric acid levels in the blood before niacin therapy (1).
The tolerable upper limit intakes are shown in the table below; they are the same among the sexes and during pregnancy or lactation. They apply to supplemental vitamin B3 for healthy individuals and not to individuals receiving the vitamin under the supervision of a healthcare provider (1).
| 1-3 years | 4-8 years | 9-13 years | 14-18 years | 18+ years |
| 10mg | 15mg | 20mg | 30mg | 35mg |
Vitamin B3 Contraindications
Vitamin B3 supplementation is contraindicated in several conditions: active peptic ulcer disease, active liver disease or liver failure, hypersensitivity or allergic reactions to vitamin B3 or its components, and arterial bleeding (2, 3).
Vitamin B3 Interactions With Medications & Alcohol
Rifater (which contains isoniazid and pyrazinamide) is a medication used for tuberculosis. Isoniazid and pyrazinamide are structural analogs of vitamin B3 and block its production from tryptophan. Isoniazid may also interfere with the vitamin’s conversion to NAD. A second-line medication for tuberculosis, ethionamide, has also been reported to cause vitamin B3 deficiency.
Individuals taking antidiabetic medications should monitor their blood glucose levels if they take high doses of vitamin B3, as they may need dose adjustments (1).
Several chemotherapeutic agents, such as fluorouracil and 6-mercaptopurine, may also lead to vitamin B3 deficiency (1, 13).
Summary
Vitamin B3 is also known as niacin; niacin is generic and refers to nicotinic acid, nicotinamide (niacinamide), and other derivatives. Vitamin B3 is found in bran, yeast, eggs, red meat, poultry, fish, peanuts, whole grains, legumes, and seeds. The amino acid tryptophan is also considered a source of niacin.
Vitamin B3 is prescribed during pellagra and may be prescribed during some cases of dyslipidemia (harmful changes in lipid profile). Pellagra is caused by severe vitamin B3 deficiency and manifests with skin, neurological, and gastrointestinal problems.
Vitamin B3 supplementation is contraindicated during active peptic ulcer disease, active liver disease, hypersensitivity reactions, and arterial bleeding. Niacin supplementation may cause adverse effects, such as flushing (a warmth sensation and skin redness), low blood pressure, increased blood sugar levels, liver injury, aggravated peptic ulcer disease, and hyperuricemia.
References
- https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/
- https://www.ncbi.nlm.nih.gov/books/NBK526107/
- https://www.ncbi.nlm.nih.gov/books/NBK541036/
- https://emedicine.medscape.com/article/126568
- https://www.medscape.com/viewarticle/niacin-and-cv-risk-should-advice-intake-change-2024a1000502
- https://www.nature.com/articles/s41591-023-02793-8
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/
- https://www.sciencedirect.com/science/article/pii/S1878747923019104
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716108
- https://www.mdpi.com/2076-3921/10/8/1315
- https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13819
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570055/
- https://www.ncbi.nlm.nih.gov/books/NBK557728/
